Secreted phosphoprotein-24 kDa (spp24) (UniProtKB, accession number: Q27967) is a glycoprotein that was first cloned from bovine bone matrix and subsequently found in the periosteum and liver, but not in the heart, lung, kidney, or spleen (Hu, B., et al., J. Biol. Chem., 270, 431-436 (1995); Erratum (corrected accession number): J. Biol. Chem., 270, 10359). It was later cloned in the mouse kidney (Okazaki, Y., et al., Nature, 420, 563-573 (2002)) and uterus (Strausberg, R., et al. Proc. Natl. Acad. Sci. USA, 99, 16899-16903 (2002)), rat liver, and human bone (Bennett, C. S., et al., Matrix Biol., 22, 641-651 (2004)). Bovine spp24 is transcribed as a 203 amino acid residue protein. The first 23 residues constitute a signal peptide, which is cleaved to produce a mature 180 amino acid residue protein with a calculated mass of 20.5 kDa and a pI of 7.9 prior to modification. The N-terminal 107 amino acid residues of the mature protein constitute a cystatin or cysteine protease inhibitor domain, initially suggesting that one physiological role of spp24 might be to inhibit the cysteine proteases, such as cathepsin K, essential for bone resorption (Hu, 1995). Small amounts of spp24 were later found in the fetuin-mineral complex (FMC), a high molecular mass complex of calcium phosphate mineral, fetuin, and matrix Gla protein (MGP) initially discovered in the serum of etidronate-treated rats (Price, P. A., et al., J. Biol. Chem., 278, 22153-22160 (2003)). Since the FMC is thought to play a critical role in inhibiting calcification of arteries and soft tissue in vivo, it was suggested that spp24, like fetuin and MGP, may inhibit calcification (Price, 2003). Alternatively, spp24, which contains a heavily phosphorylated serine-rich domain, may accumulate in bone and mineral complexes due to nonspecific ionic interactions with calcium (Hu, 1995).
Reported studies focus on the role of spp24 in the regulation of BMP bioactivity. While BMP is known to be an osteoinductive protein and can plan a role in tumor growth, functions and properties of spp24 with respect to tumor growth are otherwise largely unknown. Meanwhile, development of tumor such as cancer, particularly metastastic cancer, continues to pose major public health concerns, particularly among the aging population.
Therefore, there is a need for further development of anti-tumor compositions and methods.
The embodiments described below address the above-identified problems and needs.
For consistency, the gene (which is also known as SP2 or secreted phosphoprotein-2, vs. SP1 or osteopontin) is hereafter referred to as SPP24, while the protein containing 180 amino acid residues will be referred to as spp24 as noted in the original descriptions (Hu, 1995, Price, 2003), with amino acid residue numbers added as necessary for clarity.